Patrick G. Hogan

Household Versus Individual Approaches to Eradication of Community-Associated Staphylococcus aureus in Children: A Randomized Trial

BACKGROUND Community-associated Staphylococcus aureus infections often affect multiple members of a household. We compared 2 approaches to S. aureus eradication: decolonizing the entire household versus decolonizing the index case alone. METHODS An open-label, randomized trial enrolled 183 pediatric patients (cases) with community-onset S. aureus skin abscesses and colonization of anterior nares, axillae, or inguinal folds from 2008 to 2009 at primary and tertiary centers. Participants were randomized to decolonization of the case alone (index group) or of all household members (household group). The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily chlorhexidine body washes. Colonization of cases and subsequent skin and soft tissue infection (SSTI) in cases and household contacts were ascertained at 1, 3, 6, and 12 months. RESULTS Among 147 cases with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 50% of cases in the index group and 51% in the household group (P = 1.00). Among 126 cases completing 12-month follow-up, S. aureus was eradicated from 54% of the index group versus 66% of the household group (P = .28). Over 12 months, recurrent SSTI was reported in 72% of cases in the index group and 52% in the household group (P = .02). SSTI incidence in household contacts was significantly lower in the household versus index group during the first 6 months; this trend continued at 12 months. CONCLUSIONS Household decolonization was not more effective than individual decolonization in eradicating community-associated S. aureus carriage from cases. However, household decolonization reduced the incidence of subsequent SSTI in cases and their household contacts. CLINICAL TRIALS REGISTRATION NCT00731783.

Mupirocin and Chlorhexidine Resistance in Staphylococcus aureus in Patients with Community-Onset Skin and Soft Tissue Infections

ABSTRACT Decolonization measures, including mupirocin and chlorhexidine, are often prescribed to prevent Staphylococcus aureus skin and soft tissue infections (SSTI). The objective of this study was to determine the prevalence of high-level mupirocin and chlorhexidine resistance in S. aureus strains recovered from patients with SSTI before and after mupirocin and chlorhexidine administration and to determine whether carriage of a mupirocin- or chlorhexidine-resistant strain at baseline precluded S. aureus eradication. We recruited 1,089 patients with community-onset SSTI with or without S. aureus colonization. In addition to routine care, 483 patients were enrolled in a decolonization trial: 408 received intranasal mupirocin (with or without antimicrobial baths), and 258 performed chlorhexidine body washes. Patients were followed for up to 12 months with repeat colonization cultures. All S. aureus isolates were tested for high-level mupirocin and chlorhexidine resistance. At baseline, 23/1,089 (2.1%) patients carried a mupirocin-resistant S. aureus strain and 10/1,089 (0.9%) patients carried chlorhexidine-resistant S. aureus. Of 4 patients prescribed mupirocin, who carried a mupirocin-resistant S. aureus strain at baseline, 100% remained colonized at 1 month compared to 44% of the 324 patients without mupirocin resistance at baseline (P = 0.041). Of 2 patients prescribed chlorhexidine, who carried a chlorhexidine-resistant S. aureus strain at baseline, 50% remained colonized at 1 month compared to 48% of the 209 patients without chlorhexidine resistance at baseline (P = 1.0). The overall prevalence of mupirocin and chlorhexidine resistance is low in S. aureus isolates recovered from outpatients, but eradication efforts were less successful in patients carrying a mupirocin-resistant S. aureus strain at baseline.

A serologic correlate of protective immunity against community-onset Staphylococcus aureus infection

BACKGROUND Staphylococcus aureus is among the leading causes of human infection. Widespread drug resistance, emergence of highly virulent strains, and the ability of S. aureus to colonize >30% of the human population contribute to this organisms pathogenic success. Human serologic responses to S. aureus and their relationship to protective immunity remain incompletely defined, challenging the strategic development of efficacious vaccines. METHODS We measured humoral responses to 2 staphylococcal exotoxins, α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL; LukF-PV/LukS-PV subunits), both premier targets of current vaccine and immunotherapy development. We correlated acute and convalescent serum antibody levels with incidence of recurrent infection over 12 months follow-up in 235 children with S. aureus colonization, primary or recurrent skin and soft tissue infection, or invasive disease. RESULTS Cutaneous infection elicited transient increases in anti-Hla and anti-PVL antibodies; however, subsequent infection risk was similar between primary and recurrent cutaneous infection cohorts. Patients with invasive infections had the lowest preexisting titers against Hla and LukF but displayed the highest convalescent titers. Across cohorts, convalescent anti-Hla titers correlated with protection against subsequent S. aureus infection. CONCLUSIONS Cutaneous S. aureus infection does not reliably provoke durable, protective immune responses. This study provides the first link between protection from disease recurrence and the humoral response to Hla, a virulence factor already implicated in disease pathogenesis. These observations can be utilized to refine ongoing vaccine and immunotherapy efforts and inform the design of clinical trials.

Staphylococcus aureus Colonization in Children With Community-Associated Staphylococcus aureus Skin Infections and Their Household Contacts

OBJECTIVES To measure prevalence of Staphylococcus aureus colonization in household contacts of children with acute S aureus skin and soft tissue infections (SSTI), determine risk factors for S aureus colonization in household contacts, and assess anatomic sites of S aureus colonization in patients and household contacts. DESIGN Cross-sectional study. SETTING St Louis Childrens Hospital Emergency Department and ambulatory wound center and 9 community pediatric practices affiliated with a practice-based research network. PARTICIPANTS Patients with community-associated S aureus SSTI and S aureus colonization (in the nose, axilla, and/or inguinal folds) and their household contacts. OUTCOME MEASURES Colonization of household contacts of pediatric patients with S aureus colonization and SSTI. RESULTS Of 183 index patients, 112 (61%) were colonized with methicillin-resistant S aureus (MRSA); 54 (30%), with methicillin-sensitive S aureus (MSSA); and 17 (9%), with both MRSA and MSSA. Of 609 household contacts, 323 (53%) were colonized with S aureus: 115 (19%) with MRSA, 195 (32%) with MSSA, and 13 (2%) with both. Parents were more likely than other household contacts to be colonized with MRSA (odds ratio, 1.72; 95% CI, 1.12 to 2.63). Methicillin-resistant S aureus colonized the inguinal folds more frequently than MSSA (odds ratio, 1.67; 95% CI, 1.16 to 2.41), and MSSA colonized the nose more frequently than MRSA (odds ratio, 1.75; 95% CI, 1.19 to 2.56). CONCLUSIONS Household contacts of children with S aureus SSTI had a high rate of MRSA colonization compared with the general population. The inguinal fold is a prominent site of MRSA colonization, which may be an important consideration for active surveillance programs in hospitals.

Molecular epidemiology of Staphylococcus aureus in households of children with community-associated S aureus skin and soft tissue infections.

OBJECTIVES Although colonization traditionally is considered a risk factor for Staphylococcus aureus infection, the relationship between contemporary S aureus colonization and infection is not well characterized. We aimed to relate the presence of colonizing and disease-causing strains of S aureus within individuals and households. STUDY DESIGN In a prospective study of 163 pediatric outpatients (cases) with community-associated S aureus skin and soft tissue infections in St Louis, infection isolates were obtained from cases and colonization cultures were obtained from cases and their household contacts (n = 562). Molecular typing by repetitive sequence-based polymerase chain reaction was used to compare infecting and colonizing isolates within each case. The infecting strain from each case was compared with S aureus strains colonizing household contacts. The colonization status of cases was followed for 12 months. RESULTS A total of 27 distinct strain types were identified among the 1299 S aureus isolates evaluated. Between 1 and 6 distinct strain types were detected per household. A total of 110 cases (67%) were colonized at 1 or more body sites with the infecting strain. Of the 53 cases with an infecting strain that did not match a colonizing strain, 15 (28%) had 1 or more household contacts with a colonizing strain that matched the infecting strain. Intrafamilial strain-relatedness was observed in 105 families (64%). CONCLUSION One-third of cases were colonized with a different strain type than the strain causing the skin and soft tissue infection. Fewer than one-third of cases with discordant infecting and colonizing isolates could be linked to the strain from another household contact, suggesting acquisition from sources outside the household.

Discriminatory indices of typing methods for epidemiologic analysis of contemporary Staphylococcus aureus strains

Abstract Historically, a number of typing methods have been evaluated for Staphylococcus aureus strain characterization. The emergence of contemporary strains of community-associated S. aureus, and the ensuing epidemic with a predominant strain type (USA300), necessitates re-evaluation of the discriminatory power of these typing methods for discerning molecular epidemiology and transmission dynamics, essential to investigations of hospital and community outbreaks. We compared the discriminatory index of 5 typing methods for contemporary S. aureus strain characterization. Children presenting to St. Louis Childrens Hospital and community pediatric practices in St. Louis, Missouri (MO), with community-associated S. aureus infections were enrolled. Repetitive sequence-based PCR (repPCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal protein A (spa), and staphylococcal cassette chromosome (SCC) mec typing were performed on 200 S. aureus isolates. The discriminatory index of each method was calculated using the standard formula for this metric, where a value of 1 is highly discriminatory and a value of 0 is not discriminatory. Overall, we identified 26 distinct strain types by repPCR, 17 strain types by PFGE, 30 strain types by MLST, 68 strain types by spa typing, and 5 strain types by SCCmec typing. RepPCR had the highest discriminatory index (D) of all methods (D = 0.88), followed by spa typing (D = 0.87), MLST (D = 0.84), PFGE (D = 0.76), and SCCmec typing (D = 0.60). The method with the highest D among MRSA isolates was repPCR (D = 0.64) followed by spa typing (D = 0.45) and MLST (D = 0.44). The method with the highest D among MSSA isolates was spa typing (D = 0.98), followed by MLST (D = 0.93), repPCR (D = 0.92), and PFGE (D = 0.89). Among isolates designated USA300 by PFGE, repPCR was most discriminatory, with 10 distinct strain types identified (D = 0.63). We identified 45 MRSA isolates which were classified as identical by PFGE, MLST, spa typing, and SCCmec typing (USA300, ST8, t008, SCCmec IV, respectively); within this collection, there were 5 distinct strain types identified by repPCR. The typing methods yielded comparable discriminatory power for S. aureus characterization overall; when discriminating among USA300 isolates, repPCR retained the highest discriminatory power. This property is advantageous for investigations conducted in the era of contemporary S. aureus infections.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Isolated in Serial Cultures from the Respiratory Tract of Children with Cystic Fibrosis

Background: Little is known about strain relatedness of methicillin-resistant Staphyloccocus aureus (MRSA) isolated at serial time points from the respiratory tract of patients with cystic fibrosis (CF). The objectives are to interrogate the genetic diversity of MRSA recovered in serial cultures from children with CF and to correlate strain relatedness with clinical characteristics. Methods: We performed a retrospective analysis of children with CF from whom MRSA was isolated from serial respiratory cultures from 2005 to 2011. Within individual patients, relatedness of isolated strains was determined by repetitive-sequence polymerase chain reaction, and the staphylococcal cassette chromosome mec type of each isolate was characterized. Medical records corresponding to the MRSA cultures were reviewed. Results: We identified 54 CF patients with serial MRSA cultures (145 distinct cultures). Over time, 45 (83%) patients maintained the same strain type and 9 (17%) possessed at least 2 distinct strain types. A total of 91 pairs of isolates were analyzed for strain relatedness. Of these, 81 (89%) were identical and 10 (11%) were distinct strain types. About 117 (83%) isolates were staphylococcal cassette chromosome mec type II, 24 (17%) were staphylococcal cassette chromosome mec type IV and 4 were other types not resolvable with our assay. Clinical factors, including time interval and prescription of antibiotics effective against MRSA between positive cultures, did not correlate with acquisition of a distinct MRSA strain by individual patients. Conclusions: Our data suggest that sustained presence of MRSA in CF patients is most commonly attributable to identical strain types. Acquisition of distinct MRSA strains in the airway is infrequent.

Vitamin D Sufficiency and Staphylococcus aureus Infection in Children

Vitamin D promotes epithelial immunity by upregulating antimicrobial peptides, including LL-37, which have bactericidal activity against Staphylococcus aureus. We found that children with vitamin D deficiency or insufficiency [25-hydroxyvitamin D <30 ng/mL] were more likely to present with recurrent, rather than primary, S. aureus skin or soft tissue infection. Vitamin D sufficiency may be one of a myriad of host and environmental factors that can be directly impacted to reduce the frequency of S. aureus skin and soft tissue infection.

Diversity of Staphylococcus aureus strains colonizing various niches of the human body

OBJECTIVES As individuals may be colonized with multiple strains of Staphylococcus aureus at different body sites, the objectives of this study were to determine whether S. aureus polyclonal colonization exists within one body niche and the optimal sampling sites and culture methodology to capture the diversity of S. aureus strains in community-dwelling individuals. METHODS Swabs were collected from the nares, axillae, and inguinal folds of 3 children with community-associated S. aureus infections and 11 household contacts, all with known S. aureus colonization. S. aureus isolates were recovered from each body niche using 4 culture methods and evaluated for polyclonality using phenotypic and genotypic strain characterization methodologies. RESULTS Within individuals, the mean (range) number of phenotypes and genotypes was 2.4 (1-4) and 3.1 (1-6), respectively. Six (43%) and 10 (71%) participants exhibited phenotypic and genotypic polyclonality within one body niche, respectively. Broth enrichment yielded the highest analytical sensitivity for S. aureus recovery, while direct plating to blood agar yielded the highest genotypic strain diversity. CONCLUSIONS This study revealed S. aureus polyclonality within a single body niche. Culture methodology and sampling sites influenced the analytical sensitivity of S. aureus colonization detection and the robustness of phenotypic and genotypic strain recovery.

Molecular Epidemiology of Recurrent Cutaneous Methicillin-Resistant Staphylococcus aureus Infections in Children

We assessed the relatedness by repetitive-sequence polymerase chain reaction of isolates obtained from children with recurrent methicillin-resistant Staphylococcus aureus cutaneous infections over 6 years. Ninety percent of the cases could be attributed to recurrence of the same strain type, suggesting that optimized decolonization methods in children might effectively prevent recurrent infection.